Our basic knowledge and understanding of the mechanism by which ethanol impairs growth is meager. The proposed preliminary research is designed to investigate the possibility that ethanol retards fetal growth by altering the physiology of somatomedins\insulin-like growth factors (Sms/IGFs), a family of hormonally regulated growth factors, which play a pivotal role in the process of growth and differentiation. Presently, there is no published information concerning the effect of ethanol on Sms during fetal development. Specifically, this research is designed to evaluate aspects of Sm/IGF physiology that may be vulnerable to ethanol toxicity. The parameters to be investigated include the effects of ethanol on: 1) the capacity of fetal and postnatal tissue to synthesize and secrete Sms/IGFs; 2) Sm-carrier proteins and their capacity to bind Sm/IGF; 3) IGF I and MSA binding to receptors; and 4) the postnatal shift from the fetal (high plasma MSA) to the adult form of Sms (IGF I). The rat will be used as a model in these studies because knowledge of the rat endocrine system is extensive and because this species is vulnerable to ethanol-induced growth retardation. In in vivo studies, pregnant dams will be fed a liquid diet with 30% of the calories derived from ethanol. To enhance potential for extrapolation of results to human fetuses, ethanol exposure of pups, by means of an ethanol vapor chamber, will be extended to postnatal day 10, which corresponds to human fetal development at the end of the third trimester. To evaluate the direct effects of ethanol, studies will also be conducted in vitro. Information derived from these studies will provide a basis for more directed analysis of the role of Sms in mediating ethanol-induced fetal growth retardation.